Background: Chronic kidney disease is associated with increased rates of incidence, morbidity, and mortality in lower-extremity peripheral artery disease (PAD). No specific marker for a functional risk assessment of kidney disease in PAD is known, especially at the early stages. Thus, we speculated that urinary vanin-1 (uVNN1), a marker of oxidative stress even in early kidney injury, could further stratify outcome assessment in patients with PAD.
Methods: Patients with stable PAD (n = 304) of the Vienna medical cohort were followed up for up to 10 years and the outcome was assessed by central death database queries. uVNN1 was measured by enzyme-linked immunosorbent assay (ELISA) at study inclusion and normalized to urinary creatinine (uVNN1/Cr). During the observation time (9.3, 7.0-9.8 years), 104 patients died, 54.8% of which were due to cardiovascular causes.
Results: uVNN1/Cr was associated with a urine albumin-creatinine ratio (UACR) (R = 0.166, p = 0.004) but not with an estimated glomerular filtration rate (R = 0.102, p = 0.077). Levels of uVNN1/Cr did not differ between asymptomatic and symptomatic PAD (p = 0.406). Kaplan-Meier curves showed a clear-cut association with higher all-cause (log-rank p = 0.034) and cardiovascular mortality (log-rank p = 0.032) with higher uVNN1/Cr levels. Similarly, significant associations for all-cause (hazard ratio [HR] 1.34, 95% CI [1.08-1.67], p = 0.009) and cardiovascular mortality (HR 1.45, 95% CI [1.06-1.99], p = 0.020) could be seen in multivariable Cox regression models.
Conclusions: uVNN1/Cr showed an independent association with both all-cause and cardiovascular mortality in patients with PAD and was associated with early kidney disease. Thus, uVNN1 could be a useful marker for risk stratification of kidney disease in PAD.
Keywords: chronic kidney disease; fibrosis; inflammation; mortality; peripheral artery disease (PAD); urinary vanin-1, biomarkers.